Pneumococcal diseases are a major public health problem all over the world. Infections caused by pneumococci are a major cause of morbidity and mortality all over the world. Pneumonia, febrile bacteraemia and meningitis are the most common manifestations of invasive pneumococcal disease, whereas bacterial spread within the respiratory tract may result in middle-ear infection, sinusitis or recurrent bronchitis. Compared with invasive disease, the non-invasive manifestations are usually less severe, but considerably more common.
In spite of the importance of pneumococcal disease, there is a scarcity of information on disease burden, particularly from developing countries. This is partly due to the inherent problem of obtaining an etiological diagnosis in cases of pneumonia. However, based on available data, acute respiratory infections kill an estimated 2.6 million children under five years of age annually. The pneumococcus causes over 1 million of these deaths, most of which occur in developing countries, where the pneumococcus is probably the most important pathogen of early infancy. In Europe and the United States, pneumococcal pneumonia is the most common community-acquired bacterial pneumonia, estimated to affect approximately 100 per 100 000 adults each year. The corresponding figures for febrile bacteraemia and meningitis are 15-19 per 100 000 and 1-2 per 100 000, respectively. The risk for one or more of these manifestations is much higher in infants and elderly people, as well as immune compromised persons of any age. Even in economically developed regions, invasive pneumococcal disease carries high mortality; for adults with pneumococcal pneumonia the mortality rate averages 10%-20%, whilst it may exceed 50% in the high-risk groups. Pneumonia is by far the most common cause of pneumococcal death worldwide.
The etiological agent of pneumococcal diseases, Streptococcus pneumoniae (the pneumococcus) a Gram-positive encapsulated coccus, surrounded by a polysaccharide capsule. Differences in the composition of this capsule permit serological differentiation between about 90 capsular types, some of which are frequently associated with pneumococcal disease, others rarely. Invasive pneumococcal infections include pneumonia, meningitis and febrile bacteremia; among the common non-invasive manifestations are otitis media, sinusitis and bronchitis.
Pneumococcal resistance to essential antimicrobials such as penicillins, cephalosporins and macrolides is a serious and rapidly increasing problem worldwide.
Conditions associated with increased risk of serious pneumococcal disease include age extremes (infants, elderly) and being immunocompromised for any reason, including but not limited to: HIV infection, other chronic viral infections, sickle-cell anaemia, diabetes, cancer and cancer therapy, smoking, chronic organ failures, organ transplant and immune suppressive therapy.
The recent development of widespread microbial resistance to essential antibiotics and the increasing number of immunocompromised persons underline the urgent need for more efficient pneumococcal vaccines.
Some of the shortcomings of current vaccination include: need for several boosts to achieve protection, delay in rise of protective antibodies, prevalence of vaccine non-responders (this is particularly a problem for immune-compromised individuals), cost of antigen and vaccine production which is a very significant limitation in the development of new conjugated pneumococcal vaccines, poorly protective antibodies with low affinity, falling antibody titres over time.
An object of the new pneumococcal vaccine of the invention is to overcome at least partially some of these shortcomings. In particular with a view to vaccinate immunocompromised subjects against pneumoccocal infections.